Search Results (66)

The retinal pigment epithelium (RPE) is strongly involved in the pathogenesis of several retinal diseases, such as age-related macular degeneration (AMD). RPE models addressing specific pathological pathways are of high importance for understanding cellular pathomechanisms and pre-clinical screening of potential new therapeutics. The goal of this study is to establish standard operation protocols for single-eye porcine RPE preparation for AMD-relevant models of oxidative stress (RPE-Ox) and inflammation (RPE-Inf). Porcine primary RPE were prepared from one eye and seeded into one well of 12-well plates or, for polar differentiation, in transwell inserts. Different coatings (Poly-ᴅ-Lysine and laminin) and serum content of media (10%, 5%, and 1%) were tested to determine optimal culture parameters. For RPE-Ox, cells were treated with NaIO₃, CoCl₂, or erastin; cell viability (thiazolyl blue tetrazolium bromide, MTT), and gene expression (RT-qPCR) were determined. For RPE-Inf, cells were treated with lipopolysaccharide (LPS), polyinosinic/polycytidylic acid (Poly I:C), or tumor necrosis factor alpha (TNF-α); cell viability (MTT), cytokine secretion (ELISA), and gene expression (RT-qPCR) were determined. For transwell plates in RPE-Inf, cell viability (MTT), polar cytokine secretion (ELISA), gene expression (RT-qPCR), and transepithelial electrical resistance (TEER) for barrier assessment were conducted. For RPE-Ox, effective LD₅₀ could be achieved by using 24 h stimulation with 25 µm erastin, seven days after preparation in 5% serum cultures, without coating. For gene expression assessment, the use of Poly-ᴅ-Lysine is recommended. For RPE-Inf, three days of LPS stimulation (1 µg/mL) showed effective cytokine activation with 5% serum on uncoated 12-well plates. Transwell plates are not recommended for cytokine secretion assessment. It can be used for cell barrier assays in which LPS also showed effective cell barrier decrease and gene expression assays. Two specific best practice protocols for the use of porcine single-eye cultures in AMD research concerning oxidative stress and inflammation with optimized parameters were established and are provided. Full article

Background: Increased IL-1β levels may promote carcinogenesis and metastasis by affecting tumor biology and the tumor microenvironment (TME). In this context, extracellular vesicles (EVs) play a key role in cell-to-cell communication, thus modulating the TME and immune response. Here, we aimed to test whether tumor-derived small EVs (TEVs) isolated from sensitive and osimertinib-resistant (OR) non-small-cell lung cancer (NSCLC) cells may promote EMT via fibronectin binding to α5β1 integrin as well as suppress the immune system and if these effects may be favored by IL-1β. Methods: TEVs were isolated from control, OR, and IL-1β-stimulated NSCLC cells. Expressions of fibronectin and PD-L1 were screened in TEVs and the mRNA levels of vimentin and SMAD3 were also assessed in cancer cells after TEV co-culturing. Furthermore, to detect the effect on immune cells, we co-cultured TEVs with lung cancer patients’ peripheral blood mononuclear cells (PBMCs). Results: TEVs were positive for fibronectin and the highest protein levels were found in TEVs obtained from the OR and IL-1β-stimulated cells. TEV-mediated activation of α5β1 signaling led to the upregulation of vimentin and SMAD3 mRNA in NSCLC cells and stimulated cell migration. EVs also increased PD-1, CTLA-4, FOXP3, TNF-α, IL-12, and INF-γ mRNA in lung cancer patients’ immune cells. Conclusions: Our findings indicate that TEVs promote EMT in NSCLC cells by the activation of the fibronectin–α5β1 axis. Finally, IL-1β stimulation induces TEV release with biological properties similar to OR TEVs, thus leading to cancer invasion and immune suppression and suggesting that inflammation can promote tumor spreading. Full article

This study examined branched-chain fatty acids (BCFAs)’ effects on oxidative stress, energy metabolism, inflammation, tight junction disruption, apoptosis, and Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling in lipopolysaccharide (LPS)-induced calf small intestinal epithelial cells (CSIECs). Eight groups were used: a control group, an LPS-induced group, and six BCFA treatment groups (12-methyltridecanoic acid (iso-C14:0), 13-methyltetradecanoic acid (iso-C15:0), 14-methylpentadecanoic acid (iso-C16:0), 15-methylhexadecanoic acid (iso-C17:0), 12-methyltetradecanoic acid (anteiso-C15:0), and 14-methylhexadecanoic acid (anteiso-C17:0)) with LPS. The BCFA pretreatments significantly increased CSIEC activity compared to the LPS-induced group, with iso-C14:0 showing the highest activity (89.73%). BCFA reduced Reactive Oxygen Species (ROS) generation and malondialdehyde (MDA) levels and improved the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities and glutathione (GSH) levels. Iso-C16:0 optimized total antioxidant capacity (T-AOC). BCFA enhanced the mitochondrial membrane potential, Adenosine Triphosphate (ATP) enzyme activity, and ATP content, with iso-C14:0 increasing ATP by 27.01%. BCFA downregulated interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, and interferon (INF)-γ gene expression, reduced IL-6 levels, and increased IL-10 expression. Myeloid differentiation factor 88 (MyD88) mRNA levels were reduced. BCFA alleviated Zonula Occludin (ZO-1), Claudin-1, and Claudin-4 decrease and increased Occludin levels. BCFA mitigated LPS-induced increases in Caspase-3 and BCL2-Associated X (BAX) mRNA levels, reduced Caspase-8 and Caspase-9 expression, and increased B-Cell Lymphoma-2 (BCL-2) mRNA levels. The Entropy Weight-TOPSIS method was adopted, and it was discovered that iso-C15:0 has the best effect. In summary, BCFA supplementation mitigated oxidative stress and enhanced mitochondrial function. BCFA inhibited TLR4/NF-κB signaling pathway overactivation, regulated inflammatory cytokine gene expression, reduced cellular apoptosis, preserved tight junction integrity, and supported barrier function. Full article

Water mint (Mentha aquatica) is used in many formulations worldwide as a functional food and natural remedy to treat gastrointestinal disorders, lung diseases, and certain mental disorders such as epilepsy and depression. This study assessed the bioactivity of its infusion extract (INF) and hydroethanolic extract (HE) to highlight its health benefits. These extracts were analyzed for their chemical composition by HPLC-DAD-ESI-MSn, their antioxidant and antidiabetic properties, and their capacities to protect human erythrocytes against induced hemoglobin oxidation and lipid peroxidation. The effect on normal human dermal fibroblast (NHDF) cells and on the N27 rat dopaminergic neuron cell line was also assessed. The chromatographic analysis identified 57 compounds belonging to hydroxycinnamic acids, flavanones, flavone, and isoflavonoids. In respect to the biological potential, the Mentha aquatica extracts revealed a notable capacity for 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and superoxide radicals, as well as for the inhibition of α-glucosidase action and the protection of human erythrocytes against oxidative damage. Quantification revealed noteworthy phenolic content in both extracts. Additionally, the extracts demonstrated less cytotoxic effects regarding the NHDF and N27 cell lines. Overall, Mentha aquatica presents promising antioxidant activity and a spectrum of potential biological activities, underscoring its significance as a novel antioxidant candidate for applications in animal nutrition, human medicine, and natural product research in the pharmaceutical and nutraceutical industries. Full article

This narrative review examines lithium’s effects on immune function, inflammation and cell survival, particularly in bipolar disorder (BD) in in vitro studies, animal models and clinical studies. In vitro studies show that high lithium concentrations (5 mM, beyond the therapeutic window) reduce interleukin (IL)-1β production in monocytes and enhance T-lymphocyte resistance, suggesting a protective role against cell death. Lithium modulates oxidative stress in lipopolysaccharide (LPS)-activated macrophages by inhibiting nuclear factor (NF)-ƙB activity and reducing nitric oxide production. At therapeutically relevant levels, lithium increased both pro-inflammatory [interferon (INF)-γ, IL-8 and tumor necrosis factor (TNF)-α)] and anti-inflammatory (IL-10) cytokines on whole blood supernatant culture in healthy volunteers, influencing the balance of pro- and anti-inflammatory responses. Animal models reveal lithium’s potential to alleviate inflammatory diseases by reducing pro-inflammatory cytokines and enhancing anti-inflammatory responses. It also induces selective macrophage death in atherosclerotic plaques without harming other cells. In primary rat cerebellum cultures (ex vivo), lithium prevents neuronal loss and inhibits astroglial growth, impacting astrocytes and microglia. Clinical studies show that lithium alters cytokine profiles and reduces neuroinflammatory markers in BD patients. Chronic treatment decreases IL-2, IL-6, IL-10 and IFN-γ secretion from peripheral blood leukocytes. Lithium response correlates with TNF-α levels, with poor responders showing higher TNF-α. Overall, these findings elucidate lithium’s diverse mechanisms in modulating immune responses, reducing inflammation and promoting cell survival, with significant implications for managing BD and other inflammation-related conditions. Yet, to better understand the drug’s impact in BD and other inflammatory/neuroinflammatory conditions, further research is warranted to appreciate lithium’s therapeutic potential and its role in immune regulation. Full article

Fowl adenovirus serotype 4 (FAdV-4) outbreaks have caused significant economic losses in the Chinese poultry industry since 2015. The relationships among viral structural proteins in infected hosts are relatively unknown. To explore the role of different parts of the fiber-1 protein in FAdV-4-infected hosts, we truncated fiber-1 into fiber-1-Δ1 (73–205 aa) and fiber-1-Δ2 (211–412 aa), constructed pEF1α-HA-fiber-1-Δ1 and pEF1α-HA-fiber-1-Δ2 and then transfected them into leghorn male hepatocyte (LMH) cells. After FAdV-4 infection, the roles of fiber-1-Δ1 and fiber-1-Δ2 in the replication of FAdV-4 were investigated, and transcriptome sequencing was performed. The results showed that the fiber-1-Δ1 and fiber-1-Δ2 proteins were the shaft and knob domains, respectively, of fiber-1, with molecular weights of 21.4 kDa and 29.6 kDa, respectively. The fiber-1-Δ1 and fiber-1-Δ2 proteins were mainly localized in the cytoplasm of LMH cells. Fiber-1-Δ2 has a greater ability to inhibit FAdV-4 replication than fiber-1-Δ1, and 933 differentially expressed genes (DEGs) were detected between the fiber-1-Δ1 and fiber-1-Δ2 groups. Functional analysis revealed these DEGs in a variety of biological functions and pathways, such as the phosphoinositide 3-kinase–protein kinase b (PI3K–Akt) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, cytokine–cytokine receptor interactions, Toll-like receptors (TLRs), the Janus tyrosine kinase–signal transducer and activator of transcription (Jak–STAT) signaling pathway, the nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) signaling pathway, and other innate immune pathways. The mRNA expression levels of type I interferons (IFN-α and INF-β) and proinflammatory cytokines (IL-1β, IL-6 and IL-8) were significantly increased in cells overexpressing the fiber-1-Δ2 protein. These results demonstrate the role of the knob domain of the fiber-1 (fiber-1-Δ2) protein in FAdV-4 infection and provide a theoretical basis for analyzing the function of the fiber-1 protein of FAdV-4. Full article

Background: The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. Methods: Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56^bright, and CD56^dim NK cell subsets after in vitro stimulation. Results: The frequencies of TIGIT⁺ cells in total NK, CD56^bright, and CD56^dim NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT⁺ cells than the corresponding TIGIT⁻ cells in all HDs, whereas those for TIGIT⁺ to TIGIT⁻ cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients’ TIGIT⁺ NK cells displayed lower K562 cell-killing activity than their TIGIT⁻ NK cells. In addition, high frequencies of TIGIT⁺ cells in total NK and CD56^dim NK cells were associated with poor RFS. Conclusions: TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients. Full article

Introduction: COVID-19 is a pandemic disease and is widespread over the world. This disease shows a 5.1% mortality. The understanding of the disease has expanded rapidly in many areas, including virological, epidemiological, clinical, and management dimensions. To better understand the inflammatory and immune profiles that impact the pathogenesis and development of severe COVID-19 symptoms, further studies are essential. This research aims to explore the inflammatory and adaptive immune responses associated with COVID-19, considering factors such as genetic diversity and environmental exposure among Saudi patients. The goal is to determine if patients with severe COVID-19 exhibit different disease phenotypes. Materials and Methods: This case-control study includes 115 participants (healthy and with COVID-19 infection), 55 of which had confirmed cases of COVID-19 in intensive care units (ICUs) at different hospitals in Makkah City, Saudi Arabia. Whole blood samples were collected from June to September 2021 for cellular analyses, and inflammation marker data were collected from hospital records. The expression of activation markers on B (CD27 and CD38) and T cells (CD27 and HLA-DR) was obtained using the flow cytometry technique. Also, serum was collected for cytokine measurements, including IL-6, INF-γ, and TNF- α. Results: The results indicated that lymphopenia and excessive T cell activation were more prevalent in severe cases than in healthy individuals. Furthermore, the results revealed that severe COVID-19 patients had an increased frequency of CD19+ B cells, with changes in B cell subsets. The current study implies impairment and changes in the phenotype of adaptive cells (including T and B cells), with an increase in HLA-DR molecules and inflammation markers with pro-inflammatory cytokines in severe COVID-19 cases. Conclusions: The current study implies impairment and changes in the phenotype of adaptive cells (including T and B cells), with an increase in HLA-DR molecules and inflammation markers in severe COVID-19 cases, which could be targeted for therapeutic interventions. This might be a valuable approach for the diagnosis and treatment of severe COVID-19 cases. Full article

Objectives: Fatigue is a prominent feature of long COVID (LC) and may be related to several pathophysiologic mechanisms, including immune hyperstimulation. Aerobic endurance exercise training may be a useful therapy, with appropriate attention to preventing post-exertional malaise. Methods: Fourteen participants completed a pilot study of aerobic exercise training (twenty 1.5 h sessions of over 10 weeks). Cardiorespiratory fitness, 6 min walk distance, quality of life, symptoms, 7-day physical activity, immunophenotype, and inflammatory biomarkers were measured before and after exercise training. Results: The participant characteristics at baseline were as follows: 53.5 ± 11.6 yrs, 53% f, BMI 32.5 ± 8.4, 42% ex-smokers, 15.1 ± 8.8 months since initial COVID-19 infection, low normal pulmonary function testing, $\stackrel{.}{\mathrm{V}}$O_2peak 19.3 ± 5.1 mL/kg/min, 87 ± 17% predicted. After exercise training, participants significantly increased their peak work rate (+16 ± 20 W, p = 0.010) and $\stackrel{.}{\mathrm{V}}$O_2peak (+1.55 ± 2.4 mL/kg/min, p = 0.030). Patients reported improvements in fatigue severity (−11%), depression (−42%), anxiety (−29%), and dyspnea level (−46%). There were no changes in 6MW distance or physical activity. The circulating number of CD3+, CD4+, CD19+, CD14++CD16, and CD16++CD14+ monocytes and CD56+ cells (assessed with flow cytometry) increased with acute exercise (rest to peak) and was not diminished or augmented by exercise training. Plasma concentrations of TNF-α, IL-6, IL-8, IL-10, INF-γ, and INF-λ were normal at study entry and not affected by training. Conclusions: Aerobic endurance exercise training in individuals with LC delivered beneficial effects on cardiorespiratory fitness, quality of life, anxiety, depression, and fatigue without detrimental effects on immunologic function. Full article

Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host’s body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain oxidative stress induced by Plasmodium berghei in male mice. Two protocols were applied in this study: the therapeutic and prophylactic protocols. The results of the therapeutic protocol revealed a significant decrease in the level of parasitemia caused by P. berghei. Additionally, the histopathological changes in various brain regions were markedly improved after treatment with betalains. Regarding the prophylactic protocol, betalains were able to protect the brain tissues from oxidative stress, inflammation, and disrupted neurotransmitters expected to occur as a result of infection by P. berghei. This was demonstrated by modulating the activities of brain antioxidants (SOD and GSH), inflammatory cytokines (IL-6, IL-10, IL-12, TNF-α, and INF-γ), and neurotransmitters (serotonin, epinephrine, and norepinephrine). This study has proven that using betalains as a treatment or as a preventive has a vital and effective role in confronting the brain histopathological, oxidative stress, and inflammatory changes induced by P. berghei infection. Full article

The objective of this study was to examine the effects of varying levels of dietary chitosan supplementation on mitigating cadmium stress and its influence on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and the expression of related genes in juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). Five groups of juvenile tilapias (initial body weight 21.21 ± 0.24 g) were fed five diets with different levels (0%, 0.5%, 1.0%, 1.5%, and 2.0%) of chitosan supplementation for 60 days under cadmium stress (0.2 mg/L Cd²⁺). The findings indicated that, compared with the 0% chitosan group, dietary chitosan could significantly increase (p < 0.05) the final weight (Wf), weight gain rate (WGR), specific growth rate (SGR), daily growth index (DGI), and condition factor (CF), while the feed conversion ratio (FCR) expressed the opposite trend in juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of cholinesterase (CHE), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), and lysozyme (LZM), while glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and complement 3 (C3) in the serum of juvenile GIFT expressed the opposite trend. Dietary chitosan could significantly increase (p < 0.05) the activities of superoxide dismutase (SOD) and catalase (CAT) and significantly decrease (p < 0.05) the activities (contents) of glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in the serum of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of CAT, GST, GSH-Px, and total antioxidant capacity (T-AOC) and significantly decrease (p < 0.05) the contents of MDA in the liver of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of SOD, GSH-Px, T-AOC, Na⁺-K⁺-ATPase, and Ca²⁺-ATPase and significantly decrease (p < 0.05) the activities (contents) of CAT, GST, and MDA in the gills of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of cat, sod, gst, and gsh-px in the liver of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of interferon-γ (inf-γ) in the gills and spleen and significantly down-regulate (p < 0.05) the gene expression of inf-γ in the liver and head kidney of juvenile GIFT. Dietary chitosan could significantly down-regulate (p < 0.05) the gene expression of interleukin-6 (il-6), il-8, and tumor necrosis factor-α (tnf-α) in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of il-10 in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of transforming growth factor-β (tgf-β) in the liver and significantly down-regulate (p < 0.05) the gene expression of tgf-β in the head kidney and spleen of juvenile GIFT. In conclusion, dietary chitosan could mitigate the impact of cadmium stress on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and related gene expression in juvenile GIFT. According to the analysis of second-order polynomial regression, it was found that the optimal dietary chitosan levels in juvenile GIFT was approximately 1.42% to 1.45%, based on its impact on Wf, WGR, SGR, and DGI. Full article

Naringin is one of the common flavonoids in grapefruit, which has anti-cancer, antioxidant, and anti-inflammatory activities. However, its poor solubility limits its wide application. Therefore, the aim of this study is to investigate the anti-inflammatory effect of naringin combined with chitooligosaccharides with good biocompatibility by constructing a mouse model of systemic inflammatory response syndrome (SIRS). The results showed that the naringin–chitooligosaccharide (NG-COS) complex significantly inhibited lipopolysaccharide (LPS)-induced weight loss, reduced food intake, tissue inflammatory infiltration, and proinflammatory cytokines IL-6, TNF-α, INF-γ, and IL-1β levels. The complex also significantly affected the content of malondialdehyde and the activities of MPO, SOD, and GSH in the liver, spleen, lungs, and serum of mice with systemic inflammation. In addition, NG-COS significantly inhibited the mRNA expression of inflammatory factors in the TLR4/NF-κB signaling pathway. Principal component analysis showed that the complexes could inhibit LPS-induced systemic inflammation in mice, and the effect was significantly better than that of naringin and chitooligosaccharides alone. This study explored the synergistic effects of chitosan and naringin in reducing inflammation and could contribute to the development of novel biomedical interventions. Full article

Our previous studies have introduced osteoclasts (OCs) as major activators of NK cells. It was found that OCs exhibit the capabilities of inducing cell expansion as well as increasing the cytotoxic activity of NK cells by granule release and increasing the secretion of TNF-α and TRAIL, leading to increased lysis of tumors in short-term as well as long-term periods, respectively. OC- induced expanded NK cells were named supercharged NK cells (sNK) due to their significantly high functional activity as well as their significantly higher cell expansion rate. It is, however, unclear whether the OC-mediated effect in NK cells is specific or whether other cytotoxic immune cells can also be expanded and activated by OCs. We chose to focus on γδ T cells and pan T cells, which also include CD8+ T cells. In this paper, we report that OCs are capable of expanding and functionally activating both γδ T cells and pan T cells. Expanded γδ T and pan T cells were capable of secreting high levels of INF-γ, albeit with different dynamics to those of NK cells, and, moreover, they are unable to kill NK-specific targets. Since we used humanized-BLT (hu-BLT) mice as a model of human disease, we next determined whether NK and T cell activation through OCs is also evident in cells obtained from hu-BLT mice. Similar to humans, OCs were capable of increasing the cell expansion and secretion of IFN-γ in the culture of either NK or T cells from hu-BLT mice, providing yet further evidence that these mice are appropriate models to study human disease. Therefore, these studies indicated that CD3+ T or γδ T cells can proliferate and be supercharged by OCs similar to the NK cells; thus, they can be used individually or in combination in the cell therapy of cancers. Full article

As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs. Full article

The study aims to determine the effect of supplementation with a mixture of Curcuma longa and Rosmarinus officinalis extracts (896:19 ratio) on the expression of 15 cytokine genes in the livers of 20 castrated goat bucks. Two equal groups were created: treated and control groups. The treated group was provided a mixture (1.6 g/day/buck) for 124 days. Liver tissue samples were collected after slaughter. The gene expression was analyzed using RT-qPCR with two reference genes. Variance analysis was conducted using a model with the group fixed effect. IL-2 and IL-8 expression was below the detection level. No differences were found for IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-16, IFN-α, IFN-β, TNF-α, and CCL4 expressions, suggesting that supplementation does not activate cytokine production in the healthy hepatocytes. The treated group demonstrated lower IL-12 expression (p < 0.05) and a tendency for higher IL-18 and INF-γ (0.05 < p < 0.10) expressions, which may indicate a hypersensitivity resulting from excessive supplement dose. The increased IFN-γ expression could be caused by the increased IL-18 expression. If a small dose of extract can induce an allergic reaction in young goat bucks, it is also possible that humans may be susceptible to an overdose of curcumin and/or turmeric extracts. Full article